Chronic Granulomatous DiseasePhase 2MUNCHRNCT00578643
Matched Unrelated or Non-Genotype Identical Related Donor Transplantation For Chronic Granulomatous Disease
A Phase 2 study testing Busulfan, Alemtuzumab and Cyclophosphamide in people with Chronic Granulomatous Disease, run by Baylor College of Medicine at 1 site in United States.
Trial summary
This study is for patients with chronic granulomatous disease (CGD), which is a disorder of the immune system that puts them at risk for severe infections. CGD is caused by a genetic defect that stops or prevents the white blood cells from killing certain bacteria and fungi. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Chronic Granulomatous Disease
- What is being tested?
- Busulfan, Alemtuzumab and Cyclophosphamide
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2004to 24 Nov 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- CGD patients as documented by an abnormal NBT assay in a male patient and/or abnormal NADPH enzyme mutation confirmed by genetic analysis with abnormal NBT.
- Patients must not have an HLA genotype identical donor.
- Patients must have a 5/6 or 6/6 HLA-matched unrelated donor or a 5/6 or 6/6 HLA phenotype-matched related donor.
- Patients must have had at least one serious infection characteristic of those manifested in patients with CGD.
- Patients must not have active infection. An active infection may include the following: 1) clinical findings consistent with an infection such as fever, cavitary organ lesions, osteomyelitis; 2) progression of presumed infection based upon findings of diagnostic imaging (two or more studies at least 1 month a part).
- No cumulative organ dysfunction that, in the estimation of the treating physicians, will diminish the patient's likelihood to survive this procedure.
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- Negative pregnancy test for post-pubertal female patients.
- Echocardiogram shortening fraction >/= 28%.
- DLCO 50% or greater predicted or FEV1 >/= 50% predicted.
Who cannot join
- Active or uncontrolled infection (e.g. lung infection, cavitary organ lesions, osteomyelitis).
- Markedly elevated C reactive protein or sedimentation rate relative to patient's baseline.
- Invasive bone or bone marrow disease.
- Lack of potential hematologic blood product donors in the past (related to McLeod phenotype).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: HLA Matched Unrelated or Non-Genotype Identical Related Donor Transplantation For Chronic Granulomatous Disease
This study is for patients with chronic granulomatous disease (CGD), which is a disorder of the immune system that puts them at risk for severe infections. CGD is caused by a genetic defect that stops or prevents the white blood cells from killing certain bacteria and fungi. This condition cannot presently be cured by standard treatment with drugs or surgery. Medicine including antibiotics, antifungals, and interferon gamma, may help some patients with CGD; however even with continuous treatment, most patients with CGD will have chronic and recurrent infections. Transfusion of white blood cells may help overcome infection, but white cell transfusions lead to allergic reactions and fever and the benefit of transfusion lasts only a matter of hours. Ultimately, chronic infections can damage or injure the body organs. Injury to the lung or liver can lead to lung or liver failure and death. Medicines used to treat infection can damage body organs too. Infections may become resistant to antibiotic or antifungal treatment, and infections not responding to treatment can be deadly.
It is now known that under specific conditions and with special treatment, blood stem cells (the cells that make blood) can be transplanted from one person to another. Stem cell transplantation has been done for patients with CGD who have a healthy sibling and who share the same immune type (HLA type) as the patient. Stem cell transplantation allows healthy or normal white cells from the stem cell donor to grow or develop in the patient's bone marrow. These healthy white cells can fight infection and prevent future infections for a patient with CGD.
Read more
Patients on this study will receive stem cells from a related or unrelated donor. The donor will be closely matched to the patient's immune type but the donor is not a sibling. The reason this treatment is investigational is that we do not know the likelihood of benefit that the patient will receive. It is possible that they will have great benefit, like some of the patients who have been transplanted from a brother or sister. It is possible that the side-effects of treatment may be too severe so that the transplant won't work.
The purpose of this research study is to evaluate whether or not patients with CGD treated with a stem cell transplant from a non-matched and/or non-related donor can have a good outcome from the procedure with an acceptable number of side-effects.
Read the detailed description
In order to transplant stem cells we will need to give the patient drugs or high-dose chemotherapy to kill or destroy most of the blood forming and immune cells in the bone marrow. This is necessary to allow the donor stem cells to live and grow (engraft) in the bone marrow space. After the drug treatment is completed, the patient will be given the stem cells from the donor. The drug treatment is as follows:
Day -9 Busulfan
Day -8 Busulfan
Day -7 Busulfan
Day -6 Busulfan
Day -5 Alemtuzumab, Fludarabine, Cyclophosphamide
Day -4 Alemtuzumab, Fludarabine, Cyclophosphamide
Day -3 Alemtuzumab, Fludarabine, Cyclophosphamide
Day -2 Alemtuzumab, Fludarabine, Cyclosporine, Cyclophosphamide
Day -1 REST
Day 0 Stem cell infusion
The day after the chemotherapy treatment is completed, the patient will receive the healthy stem cells by vein, like a blood transfusion. Once in the bloodstream, the marrow cells will go to the bone marrow and grow.
It is also possible that if the marrow takes, it will cause a disease known as graft-versus-host disease (GVHD). To prevent GVHD, we will give the patient cyclosporine and Methotrexate. Methotrexate will be administered on Days 1, 3, 6 and 11 after the transplant. The cyclosporine therapy will continue for a longer period of time, however if the patient does not develop GVHD, it will be discontinued by 6 months after the stem cell transplant.
- Conditions
- Chronic Granulomatous Disease
- Being tested
- Busulfan, Alemtuzumab, Cyclophosphamide, Fludarabine, Cyclosporine
- Keywords
- Stem Cell Transplant, Chronic Granulomatous Disease, Fludarabine, Busulfan, Cyclophosphamide
- Medical subject headings
- Granulomatous Disease, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BusulfanDrug
Also called Busulfex
Days -9 through -6
1 mg/kg initially (based on weight)
AlemtuzumabBiological
Also called Campath
Day -5 through Day -2
Dose is based on weight:
Less than 15 kg: 3 mg
More than 15 kg to 30 kg: 5 mg
More than 30 kg: 15 mg
CyclophosphamideDrug
Also called Cytoxan
Days -5 through -2
50 mg/kg
FludarabineDrug
Also called Fludara
Day -5 through Day -2
30 mg/m^2
CyclosporineDrug
Also called Sandimmune
Cyclosporine will be administered beginning Day -2. Initial dose will 5 mg/kg infused over 24 hours.
Stem Cell InfusionProcedure or surgery
Stem Cell: Either bone marrow, cord blood, or peripheral blood stem cells may be used for stem cell transplantation. It is desired to infuse: for bone marrow, nucleated cells ≥ 4 X 10^8/kg recipient weight; for cord blood ≥ 3 X 10^7/kg nucleated cells; for peripheral blood stem cells ≥ 1 X 10^/kg CD34+ cells.
| Study group | Role | What they receive |
|---|---|---|
| Allogeneic unrelated transplant | Experimental | Conditioning from Day -9 to Day -1. Stem cells given on Day 0. Busulfan, alemtuzumab, cyclophosphamide, fludarabine, cyclosporine, stem cell infusion. Receives: Drug: Busulfan; Biological: Alemtuzumab; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Cyclosporine; Procedure: Stem Cell Infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Engraftment
To estimate the engraftment rate for patients with CGD using busulfan, cyclophosphamide, fludarabine and alemtuzumab (Campath 1H) as conditioning therapy for SCT from 5/6 or 6/6 HLA-matched unrelated or 5/6 or 6/6 HLA phenotype-matched related donors.
Measured: 28 days post transplant
Secondary outcomes (3)
Number of Patients That Have Complete Donor Chimerism After Transplant.
To estimate the likelihood of complete donor chimerism for patients with CGD using busulfan, cyclophosphamide, fludarabine and alemtuzumab (Campath 1H) as conditioning therapy for SCT from 5/6 or 6/6 HLA-matched unrelated or 5/6 or 6/6 HLA phenotype-matched related donors.
Measured: 120 days post transplant
Number of Patients That Have Acute GVHD and Regimen Related Morbidity/Mortality Post Transplant.
To estimate the risk for acute GVHD and regimen related morbidity/mortality for patients with CGD following stem cell transplant from 5/6 or 6/6 HLA matched unrelated or 5/6 or 6/6 HLA phenotype matched related donors.
Measured: Assessed between day 0 and day 100 post transplant
Number of Patients That Have Chronic GVHD and Regimen Related Morbidity/Mortality Post Transplant.
To estimate the risk for chronic GVHD and regimen related morbidity/mortality for patients with CGD following stem cell transplant from 5/6 or 6/6 HLA matched unrelated or 5/6 or 6/6 HLA phenotype matched related donors.
Measured: Assessed between day 100 and day 365 post transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Dec 2007 (estimated)
- Study startMar 2004
- Primary completion31 Jul 2017
- Study completion24 Nov 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Chronic Granulomatous DiseaseStudies of the same condition, open and under way.
- More trials run by Baylor College of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baylor College of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Robert Krance, Baylor College of Medicine
- Investigators
- Robert Krance, MD, Principal investigator, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00578643
- Sponsor's protocol ID
- 14771-MUNCHR
- Acronym
- MUNCHR
- Status last verified
- Oct 2018
- First submitted
- 19 Dec 2007
- Last updated
- 9 Nov 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 9 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- HLA Matched Unrelated or Non-Genotype Identical Related Donor Transplantation For Chronic Granulomatous Disease
- ClinicalTrials.gov ID
- NCT00578643
- Acronym / sponsor ID
- MUNCHR / 14771-MUNCHR
- Conditions
- Chronic Granulomatous Disease
- Keywords
- Stem Cell Transplant, Chronic Granulomatous Disease, Fludarabine, Busulfan, Cyclophosphamide
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Baylor College of MedicineUniversity, hospital or other
- Study start
- Mar 2004
- Primary completion
- 31 Jul 2017 (actual)
- Study completion
- 24 Nov 2017 (actual)
- First posted
- 21 Dec 2007 (estimated)
- Results
- Posted 9 Nov 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is for patients with chronic granulomatous disease (CGD), which is a disorder of the immune system that puts them at risk for severe infections. CGD is caused by a genetic defect that stops or prevents the white blood cells from killing certain bacteria and fungi. This condition cannot presently be cured by standard treatment with drugs or surgery. Medicine including antibiotics, antifungals, and interferon gamma, may help some patients with CGD; however even with continuous treatment, most patients with CGD will have chronic and recurrent infections. Transfusion of white blood cells may help overcome infection, but white cell transfusions lead to allergic reactions and fever and the benefit of transfusion lasts only a matter of hours. Ultimately, chronic infections can damage or injure the body organs. Injury to the lung or liver can lead to lung or liver failure and death. Medicines used to treat infection can damage body organs too. Infections may become resistant to antibiotic or antifungal treatment, and infections not responding to treatment can be deadly.
It is now known that under specific conditions and with special treatment, blood stem cells (the cells that make blood) can be transplanted from one person to another. Stem cell transplantation has been done for patients with CGD who have a healthy sibling and who share the same immune type (HLA type) as the patient. Stem cell transplantation allows healthy or normal white cells from the stem cell donor to grow or develop in the patient's bone marrow. These healthy white cells can fight infection and prevent future infections for a patient with CGD.
Patients on this study will receive stem cells from a related or unrelated donor. The donor will be closely matched to the patient's immune type but the donor is not a sibling. The reason this treatment is investigational is that we do not know the likelihood of benefit that the patient will receive. It is possible that they will have great benefit, like some of the patients who have been transplanted from a brother or sister. It is possible that the side-effects of treatment may be too severe so that the transplant won't work.
The purpose of this research study is to evaluate whether or not patients with CGD treated with a stem cell transplant from a non-matched and/or non-related donor can have a good outcome from the procedure with an acceptable number of side-effects.
Detailed description
In order to transplant stem cells we will need to give the patient drugs or high-dose chemotherapy to kill or destroy most of the blood forming and immune cells in the bone marrow. This is necessary to allow the donor stem cells to live and grow (engraft) in the bone marrow space. After the drug treatment is completed, the patient will be given the stem cells from the donor. The drug treatment is as follows:
Day -9 Busulfan
Day -8 Busulfan
Day -7 Busulfan
Day -6 Busulfan
Day -5 Alemtuzumab, Fludarabine, Cyclophosphamide
Day -4 Alemtuzumab, Fludarabine, Cyclophosphamide
Day -3 Alemtuzumab, Fludarabine, Cyclophosphamide
Day -2 Alemtuzumab, Fludarabine, Cyclosporine, Cyclophosphamide
Day -1 REST
Day 0 Stem cell infusion
The day after the chemotherapy treatment is completed, the patient will receive the healthy stem cells by vein, like a blood transfusion. Once in the bloodstream, the marrow cells will go to the bone marrow and grow.
It is also possible that if the marrow takes, it will cause a disease known as graft-versus-host disease (GVHD). To prevent GVHD, we will give the patient cyclosporine and Methotrexate. Methotrexate will be administered on Days 1, 3, 6 and 11 after the transplant. The cyclosporine therapy will continue for a longer period of time, however if the patient does not develop GVHD, it will be discontinued by 6 months after the stem cell transplant.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Allogeneic unrelated transplant | Experimental | Drug: Busulfan, Biological: Alemtuzumab, Drug: Cyclophosphamide, Drug: Fludarabine, Drug: Cyclosporine, Procedure: Stem Cell InfusionConditioning from Day -9 to Day -1. Stem cells given on Day 0. Busulfan, alemtuzumab, cyclophosphamide, fludarabine, cyclosporine, stem cell infusion. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- CGD patients as documented by an abnormal NBT assay in a male patient and/or abnormal NADPH enzyme mutation confirmed by genetic analysis with abnormal NBT.
- Patients must not have an HLA genotype identical donor.
- Patients must have a 5/6 or 6/6 HLA-matched unrelated donor or a 5/6 or 6/6 HLA phenotype-matched related donor.
- Patients must have had at least one serious infection characteristic of those manifested in patients with CGD.
- Patients must not have active infection. An active infection may include the following: 1) clinical findings consistent with an infection such as fever, cavitary organ lesions, osteomyelitis; 2) progression of presumed infection based upon findings of diagnostic imaging (two or more studies at least 1 month a part).
Key exclusion criteria (4 listed)
- Active or uncontrolled infection (e.g. lung infection, cavitary organ lesions, osteomyelitis).
- Markedly elevated C reactive protein or sedimentation rate relative to patient's baseline.
- Invasive bone or bone marrow disease.
- Lack of potential hematologic blood product donors in the past (related to McLeod phenotype).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BusulfanAlso: BusulfexDays -9 through -6 1 mg/kg initially (based on weight) | Drug | Allogeneic unrelated transplant |
| AlemtuzumabAlso: CampathDay -5 through Day -2 Dose is based on weight: Less than 15 kg: 3 mg More than 15 kg to 30 kg: 5 mg More than 30 kg: 15 mg | Biological | Allogeneic unrelated transplant |
| CyclophosphamideAlso: CytoxanDays -5 through -2 50 mg/kg | Drug | Allogeneic unrelated transplant |
| FludarabineAlso: FludaraDay -5 through Day -2 30 mg/m^2 | Drug | Allogeneic unrelated transplant |
| CyclosporineAlso: SandimmuneCyclosporine will be administered beginning Day -2. Initial dose will 5 mg/kg infused over 24 hours. | Drug | Allogeneic unrelated transplant |
| Stem Cell InfusionStem Cell: Either bone marrow, cord blood, or peripheral blood stem cells may be used for stem cell transplantation. It is desired to infuse: for bone marrow, nucleated cells ≥ 4 X 10^8/kg recipient weight; for cord blood ≥ 3 X 10^7/kg nucleated cells; for peripheral blood stem cells ≥ 1 X 10^/kg CD34+ cells. | Procedure or surgery | Allogeneic unrelated transplant |
Primary outcome
Percentage of Participants With Engraftment
Time frame: 28 days post transplant
To estimate the engraftment rate for patients with CGD using busulfan, cyclophosphamide, fludarabine and alemtuzumab (Campath 1H) as conditioning therapy for SCT from 5/6 or 6/6 HLA-matched unrelated or 5/6 or 6/6 HLA phenotype-matched related donors.
3 secondary outcomes
Number of Patients That Have Complete Donor Chimerism After Transplant.
Time frame: 120 days post transplant
Number of Patients That Have Acute GVHD and Regimen Related Morbidity/Mortality Post Transplant.
Time frame: Assessed between day 0 and day 100 post transplant
Number of Patients That Have Chronic GVHD and Regimen Related Morbidity/Mortality Post Transplant.
Time frame: Assessed between day 100 and day 365 post transplant
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Nov 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert Krance, MD principal investigator
Baylor College of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Busulfan, Alemtuzumab and Cyclophosphamide in people with Chronic Granulomatous Disease, run by Baylor College of Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Nov 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Engraftment (time frame: 28 days post transplant). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Nov 2018.